Homeostatic mechanisms play an essential role in synaptic function. They are required for the stability of neural networks and play a role in learning and memory. It is suspected that they may compensate for various disease processes, such as myasthenia gravis, and might underlie the efficacy of drugs such as antidepressants. One model system in which homeostasis can be studied is the Drosophila neuromuscular junction. At this synapse, a decrease in the post-synaptic sensitivity to neurotransmitter results in a compensatory increase in pre-synaptic transmitter release. However, little is known about the nature or molecular components of this mechanism. It is not known whether the signal is synapse specific or a more global phenomenon, nor is it known whether this phenomenon occurs only during a critical period of development or also occurs at more mature synapses. The proposed experiments will elucidate these spatial and temporal features of this mechanism. The molecular mechanism will be further probed through the characterization of a novel mutation that disrupts this homeostatic response.